[Genetic and phenotypic analysis of a patient with phosphogylcerate dehydrogenase deficiency]

Area of Science:

• Genetics
• Ophthalmology
• Metabolic disorders

Background:

• Ocular anomalies, microcephaly, and growth retardation can indicate underlying genetic conditions.
• Persistent pupillary membrane, iris coloboma, macular dysplasia, and retinal pigmentation are significant ocular findings.

Purpose of the Study:

• To investigate the genetic cause of a child presenting with microcephaly, growth retardation, intrauterine growth restriction, and ocular abnormalities.
• To identify specific gene variants responsible for the observed phenotype.

Main Methods:

• Comprehensive ophthalmologic examinations were performed, including fundus photography and fluorescein angiography.
• Whole exome sequencing was conducted on the patient and her parents.
• Candidate variants were confirmed using Sanger sequencing and bioinformatic analysis.

Main Results:

• The patient exhibited bilateral persistent pupillary membrane, inferior iris coloboma, macular dysplasia, and radial retinal pigmentation.
• Compound heterozygous missense variants (c.196G>A and c.1177G>A) in the PHGDH gene were identified, inherited from each parent.
• Bioinformatic analysis indicated that both PHGDH variants are likely pathogenic.

Conclusions:

• The patient was diagnosed with phosphoglycerate dehydrogenase deficiency.
• This case expands the phenotypic spectrum of phosphoglycerate dehydrogenase deficiency to include significant ocular manifestations.
• Identifying the genetic basis is crucial for understanding and managing this rare metabolic disorder.